The Human BioMolecular Research Institute (HBRI) is a 501(c)3 tax-exempt non-profit research institute doing basic research for the public good. HBRI was founded in December of 1997.
The research programs at HBRI are focused on unlocking biological and chemical principles related to diseases of the human body. Included in the areas of study are the use of stem cells to usher in new approaches to regenerative medicines for cardiovascular disease, neurological disease, cancer and bone diseases. Previous studies in Alzheimer’s disease and related neurodegenerative disorders, Parkinson’s disease, ALS, depression, neuroprotection, drug and alcohol abuse, pain and smoking cessation has resulted in numerous advances in medications development. The institute conducts fundamental studies of human disorders and translates findings into new drug development to address human illness. In addition, the institute promotes scientific learning through community service and public access by disseminating information and sharing research with collaborators, colleagues and the public.
“Where Medications Begin”
BREAKING NEWS:
Reengineering mexiletine by chemical synthesis to decrease toxicity and improve pharmacological properties with patient-derived iPSC cardiomyocytes.
In the United States, almost one million individuals are hospitalized every year for cardiac arrhythmias, making arrhythmias one of the top causes of healthcare expenditures with a direct cost of almost $50 billion annually. In the United States, almost 300,000 individuals die of sudden arrhythmic death syndrome every year.
Ventricular cardiac arrhythmia arises in acquired or congenital heart disease. Arrhythmias are very common in older adults but unfortunately, drugs to treat arrhythmias have liabilities. In addition, numerous investigational drugs have been withdrawn from the market because they induce QT prolongation and a potentially fatal ventricular tachycardia, a condition called Torsade de Pointes. For normal heart cell function, sodium channels rapidly inactivate with depolarization.
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Human-induced pluripotent stem cell-derived cardiomyocytes: Cardiovascular properties and metabolism and pharmacokinetics of deuterated mexiletine analogs
In the United States, almost one million individuals are hospitalized every year for cardiac arrhythmias, making arrhythmias one of the top causes of healthcare expenditures with a direct cost of almost $50 billion annually. Almost 300,000 individuals die of sudden arrhythmic death syndrome every year.
Ventricular cardiac arrhythmia arises in acquired or congenital heart disease. Arrhythmias are very common in older adults but unfortunately, drugs to treat arrhythmias have liabilities. In addition, numerous investigational drugs have been withdrawn from the market because they induce QT prolongation and a potentially fatal ventricular tachycardia, a condition called Torsade de Pointes.
Read the full press release here
Human iPSC-derived Cardiomyocytes and Pyridyl-Phenyl Mexiletine Analogs
In the United States, almost one million individuals are hospitalized every year for cardiac arrhythmias, making arrhythmias one of the top causes of healthcare expenditures with a direct cost of almost $50 billion annually. Almost 300,000 individuals die of sudden arrhythmic death syndrome every year.
Ventricular cardiac arrhythmia arises in acquired or congenital heart disease. Arrhythmias are very common in older adults but unfortunately, drugs to treat arrhythmias have liabilities. In addition, numerous investigational drugs have been withdrawn from the market because they induce QT prolongation and a potentially fatal ventricular tachycardia, a condition called Torsade de Pointes. For normal heart cell function, sodium channels rapidly inactivate with depolarization. In depolarization of cardiomyocytes, sodium channels open briefly and allow influx of sodium. Correct regulation of ion currents in cardiomyocytes is key for proper heart function.
Read the full press release here
Anti-Arrhythmic Hit to Lead Refinement in a Dish using Patient-Derived iPSCs
In the United States, almost one million individuals are hospitalized every year for cardiac arrhythmias, making arrhythmias one of the top causes of healthcare expenditures with a direct cost of almost $50 billion annually. Almost 300,000 individuals die of sudden arrhythmic death syndrome every year.
Medicinal chemists at the Human BioMolecular Research Institute (HBRI), in San Diego, CA, and stem cell biologists at Stanford University, in Stanford, CA, and cardiovascular pharmacologists at UCLA in Los Angeles, CA and Columbia University, in New York City, NY, respectively, reported on reengineered mexiletine compounds that showed improved potency and decreased toxicity in addressing ventricular cardiac arrhythmia.
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CIRM funded study uses drug development in a dish for treatment of heart arrhythmias
The Conrad Prebys Foundation funds the Human BioMolecular Research Institute to research a drug candidate to fight drug-resistant pancreatic cancer!
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Molecules, Stress Signaling and Wnt Responsiveness
Small molecules are important in chemical genetics exploration of intracellular pathways involved in normal and pathological processes. Wnt signaling plays a central role in tissue maintenance and cancer. This report showed a mechanism by which mitotic and genotoxic stress modulates Wnt responsiveness to control cell shape and renewal. The paper was featured in the journal Cell Chemical Biology.
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Molecules, Stem Cells and Bone Growth
Small molecule with an appropriate scaffold potently induced mesenchymal stem cells to generate bone cells useful for spinal fusion. The paper was featured in Tissue Engineering
San Diego, California – December, 2020. Medicinal chemists and biologists at the Human BioMolecular Research Institute (HBRI), in San Diego, CA, and University of California, San Diego (UCSD), in San Diego, CA, respectively, have reported on a technology to robustly produce human bone cells from stem cells. This may have importance for spinal fusion and addressing other bone cell disease drug discovery efforts.
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“Pancreatic cancer drug-sensitivity predicted by synergy of PAWI-2 and protein biomarker expression”
Potent inhibitor of pancreatic cancer stem cells that synergizes current standard of care, PAWI-2 is featured in Investigational New Drugs.
San Diego, Calif., September 16, 2020 – Researchers at the Human BioMolecular Research Institute and ChemRegen, Inc., reported that a small molecule potently inhibited pancreatic cancer stem cells and also synergized standard of care drugs. Publishing September 15, 2020, in the journal Investigational New Drugs, the team describes how they tested PAWI-2, a man-made, drug-like chemical that can be used to inhibit pancreatic cancer stem cells and other cancer. The researchers discovered PAWI-2 acted as a synergist to make heretofore poorly potent drugs that previously did not show much efficacy in humans work much better in in vitro studies.
Featured on The Official Blog of CIRM, California’s Stem Cell Agency:
Reengineering a drug guided by patient-derived hiPSC-cardiomyocytes
San Diego, California – September, 2020. Medicinal chemists at the Human BioMolecular Research Institute (HBRI), in San Diego, CA, and biologists at Sanford-Burnham-Prebys Medical Discovery Institute (SBPMDI), in San Diego, CA, and at Stanford University, Stanford, CA, Columbia University, New York, NY, and Northwestern University, Chicago, IL, respectively, have reported on improving an antiarrhythmic drug using patient-derived human induced pluripotent stem cell cardiomyocytes (hiPSC-CMs) in a high throughput manner in vitro. This may have importance for heart disease and other drug discovery efforts.
Reengineering a drug guided by patient-derived hiPSC-cardiomyocytes PR
https://blog.cirm.ca.gov/2020/09/16/precision-guided-therapy-from-a-patients-own-cells/
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